Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities

Abstract

SignificanceEliminating malaria from islands should, in theory, be easier than eliminating malaria from countries in mainland Africa because of restricted movement of insects and people between treated and untreated areas. The example of Bioko Island, where the entomological inoculation rate in 2004 was among the highest in Africa, demonstrates how difficult this can be. Vector control has eliminated two of the four vector species, and malaria has been dramatically reduced. This study demonstrates rapid evolution of resistance following reintroduction of pyrethroid-based control interventions, with the selection of a P450-based mechanism (CYP9K1). Urban malaria, movement of infected people from the mainland, and selection of this pyrethroid-resistance mechanism in addition to knockdown resistance has impeded progress and forced a change to nonpyrethroid indoor residual spraying.

Whole genome sequencing reveals high complexity of copy number variation at insecticide resistance loci in malaria mosquitoes

“…Finally, Cyp9k1 was the most widely amplified gene of the five, with CNVs found in over half of the populations in our dataset. Cyp9k1 is up-regulated in mosquitoes resistant to pyrethroids and DDT [44,45,48], and metabolises deltamethrin [35]. Furthermore, a selective sweep in the Cyp9k1 region has been associated with insecticide resistance in An.…”

“…gambiae and An. coluzzii, the most import metabolic genes that have been identified as major insecticide resistance candidates to date are Gste2 [28], Cyp6p3 [29,30], Cyp6m2 [29,31,32], Cyp6z1 [33] and Cyp9k1 [34,35]. If…”

Assessing connectivity despite high diversity in island populations of a malaria mosquito

“…We found two sweeps on insecticide-related genes that are common targets of selection elsewhere but which have incompletely colonized the Ssese Islands: one on cytochrome P450 monooxygenase Cyp9K1 [44, 45] present on some islands, and another on glutathione Stransferase genes ( Gste1-Gste7 ; [46–49]) at extremely low frequency on the islands. That the selective sweeps targeting these loci [4] have not fully colonized the islands despite the advantage in detoxifying pyrethroids and DDT suggests a lack of contemporary exchange.…”

Mapping Trends in Insecticide Resistance Phenotypes in African Malaria Vectors

“…Sources of insecticides in the environment include the application of insecticide-based vector control interventions for public health, such as LLINs and IRS, and the application of agricultural insecticides, which include the same insecticide classes as those used in vector control 11 . Several studies have demonstrated a local increase in insecticide resistance in field mosquito populations following the implementation of LLINs, IRS, or both 12, 13, 14, 15, 16 although in other locations evidence of higher resistance after the introduction these interventions was not found 12, 17 . Associations between agricultural pesticide use and insecticide resistance have also been found 11, 18 , and there is evidence that pesticide contamination of water bodies is a source of selection pressure for resistance acting on mosquito larvae 19 .…”